Chemical Approaches to DNA Nanotechnology

http://www3.interscience.wiley.com/cgi-bin/fulltext/122579503/PDFSTART

Diagnosing lung cancer in exhaled breath using gold nanoparticles

Conventional diagnostic methods for lung cancer1,2 are unsuitable
for widespread screening2,3 because they are expensive and
occasionally miss tumours. Gas chromatography/mass spectrometry
studies have shown that several volatile organic compounds,
which normally appear at levels of 1–20 ppb in healthy
human breath, are elevated to levels between 10 and 100 ppb in
lung cancer patients4–6. Here we show that an array of sensors
based on gold nanoparticles can rapidly distinguish the breath
of lung cancer patients from the breath of healthy individuals in
an atmosphere of high humidity. In combination with solidphase
microextraction7, gas chromatography/mass spectrometry
was used to identify 42 volatile organic compounds
that represent lung cancer biomarkers. Four of these were
used to train and optimize the sensors, demonstrating good
agreement between patient and simulated breath samples.
Our results show that sensors based on gold nanoparticles
could form the basis of an inexpensive and non-invasive diagnostic
tool for lung cancer.

Artificial reporter gene providing MRI contrast based on proton exchange

Existing magnetic resonance reporter genes all rely on the
presence of (super)paramagnetic substances and employ water
relaxation to gain contrast. We designed a nonmetallic,
biodegradable, lysine rich–protein (LRP) reporter, the prototype
of a potential family of genetically engineered reporters
expressing artificial proteins with frequency-selective contrast.
This endogenous contrast, based on transfer of radiofrequency
labeling from the reporter’s amide protons to water protons, can
be switched on and off.

Imaging the Beta-Cell Mass: Why and How

Diabetes is a disorder characterized by beta-cell loss or exhaustion
and insulin deficiency. At present, knowledge is
lacking on the underlying causes and for the therapeutic recovery
of the beta-cell mass. A better understanding of diabetes
pathogenesis could be obtained through exact monitoring
of the fate of beta-cells under disease and therapy
conditions. This could pave the way for a new era of intervention
by islet replacement and regeneration regimens.
Monitoring the beta-cell mass requires a reliable method for
noninvasive in vivo imaging. Such a method is not available at
present due to the lack of a beta-cell-specific contrast agent.
The only existing method to monitor islet cells in vivo consists
of labeling islet transplants with iron nanoparticles prior
to transplantation and visualization of the transplanted islets
by magnetic resonance imaging (MRI). Therefore, accurate
assessment of the native beta-cell mass is still limited to autopsy
studies. Endeavors to find a biological structure specific
for beta-cells led to the discovery of potential candidates
that have been tested for noninvasive imaging. Among
them are the ligand to the vesicular monoamine transporter
type 2 (VMAT-2), which is called dihydrotetrabenazine
(DTBZ), antibodies to zinc transporter (ZnT-8) and the
monoclonal antibody IC2. While DTBZ and antibodies to
ZnT-8 showed binding activities to more than beta-cells, the
anti-IC2 monoclonal antibody showed binding properties
exclusively to insulin-producing beta-cells. This effect was
demonstrated in many previous investigations, and has been
further substantiated more recently. Thus, at present, IC2
seems to be the only useful marker for noninvasive functional
imaging of native beta-cells. Experiments with a radioisotope-
chelated IC2 structure on pancreas ex vivo
showed that the tracer specifically bound to the beta-cell
surface and could be detected by nuclear imaging. In the
near future, these promising findings may offer a new way
to monitor the beta-cell mass in vivo under disease and therapy
conditions so that we can learn more about diabetes
pathogenesis and options for disease prevention.
Keywords: diabetes · beta-cell · noninvasive imaging ·
IC2 · islet transplantation · MRI · PET · photoacoustic